Infliximab ameliorates AD-associated object recognition memory impairment

Dysfunctions in the perirhinal cortex (PRh) are associated with visual recognition memory deficit, which is frequently detected in the early stage of Alzheimer's disease. Muscarinic acetylcholine receptor-dependent long-term depression (mAChR-LTD) of synaptic transmission is known as a key pathway in eliciting this type of memory, and Tg2576 mice expressing enhanced levels of A beta oligomers are found to have impaired mAChR-LTD in this brain area at as early as 3 months of age. We found that the administration of A beta oligomers in young normal mice also induced visual recognition memory impairment and perturbed mAChR-LTD in mouse PRh slices. In addition, when mice were treated with infliximab, a monoclonal antibody against TNF-alpha, visual recognition memory impaired by pre administered A beta oligomers dramatically improved and the detrimental A beta effect on mAChR-LTD was annulled. Taken together, these findings suggest that A beta-induced inflammation is mediated through TNF-alpha signaling cascades, disturbing synaptic transmission in the PRh, and leading to visual recognition memory deficits. (C) 2016 Elsevier B.V. All rights reserved.